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FLASH GENE

Symbol

ERRFI1

contributors: mct/np - updated : 10-04-2019

HGNC name	ERBB receptor feedback inhibitor 1
HGNC id	18185

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   moderately   liver       highly   pancreas exocrine       moderately   stomach       highly Endocrine thyroid       highly Hearing/Equilibrium ear       moderately Reproductive female system uterus     moderately Respiratory lung       moderately   respiratory tract trachea     moderately Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     moderately Connective bone     moderately

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an Ack homology domain containing the previously identified EGFR binding domain
	Cdc42/Rac interaction and binding (CRIB) domain

HOMOLOGY

interspecies

ortholog to murine Errfi (82.4pc)

Homologene

FAMILY

MIG6 family

CATEGORY

adaptor , regulatory , tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	multiadaptor protein may be involved in the regulation of RTK and stress signaling
	acting as a Rho GTPase activator
	involved in response to stress
	inhibiting EGFR autophosphorylation
	specifically blunting epidermal growth factor (EGF)-induced activation and/or phosphorylation of Ras, ERK, JNK, Akt/PKB, and retinoblastoma protein
	negative regulator of EGFR signaling in skin morphogenesis and is a novel tumor suppressor of EGFR-dependent carcinogenesis
	immediate early response gene encoding a nonkinase scaffolding adaptor protein (Zhang 2007)
	may play important roles in regulating stress response, maintaining homeostasis in tissues like joints or cardiac muscle, and functioning as a tumor suppressor (Zhang 2007)
	negative regulator of epidermal growth factor (EGF) signaling (Zhang 2007)
	tumor-suppressor gene (Zhang 2007)
	critical regulator of the response of the endometrium to Estrogen in regulating tissue homeostasis (Jeong 2009)
	functions to suppress the malignant potential of Glioblastoma multiforme cells by enhancing EGFR trafficking into late endosomes/lysosomes and promoting its degradation (Ying 2010)
	functions via STX8 to enhance EGF-induced receptor degradation by regulating the trafficking of internalized EGFR into late endosomes and subsequent lysosomes (Ying 2010)
	induces premature senescence via functioning in regulation of cellular senescence in normal diploid fibroblasts
	is a cytosolic multiadaptor protein that is best known for its role as a negative feedback regulator of epidermal growth factor receptor (EGFR) mediated signalling
	involvement in hepatic insulin resistance
	may regulate cell proliferation and the cell cycle through the P-ERK/CCND1 pathway
	is an adaptor protein with multiple cellular functions
	is a proximal regulator of DNA damage response (DDR) that promotes DNA repair
	is an important tumor suppressor that binds to and negatively regulates epidermal growth factor receptor (EGFR)
	EGFR-independent function for ERRFI1 as an integral component of the cell cycle machinery
	critical role of ERRFI1 in cell cycle progression that is likely to contribute to its potent tumor-suppressive properties

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	ligand-activated epidermal growth factor receptor (EGFR)
	ErbB-4 and ErbB-2.ErbB-3 dimers
	interacts with and inhibits the kinase domains of EGFR and ERBB2
	interacts with and inhibits the kinase domains of EGFR and ERBB2 (Zhang 2007)
	strong interaction with STX8 upon ligand activation therefore ensures recruitment of internalized EGFR to late endosomes and subsequently the lysosomal degradation compartment (Ying 2010)
	CHEK1 phosphorylates ERRFI1 on Ser 251, resulting in the inhibition of ERRFI1, and CHEK1 acts as a positive regulator of EGF signalling
	sustained production of ERRFI1 protein exacerbates ER stress-induced beta-cell death
	SPRY2 and ERRFI1 are important regulators of wild-type and mutant EGFR trafficking
	participates in the regulation of cell senescence and RB1 protein phosphorylation
	has an important role in the regulation of cholesterol homeostasis and bile acid synthesis
	is an important mediator of progesterone (P4) signaling to inhibit estrogen (E2) signaling in the uterus
	DNAJB1 is a novel ERRFI1-interacting protein, and DNAJB1 positively regulates the epidermal growth factor receptors (EGFR) signaling pathway via destabilization of ERRFI1
	is a negative regulator of EGF signaling
	bind to and inhibit the Rho GTPase CDC42 to suppress cytoskeletal rearrangement
	may regulate the targeting of ABL1 to chromatin
	ERRFI1 is required for inhibition of CDK1 upon DNA damage and subsequent G2/M cell cycle arrest
	controls mitotic progression and the G2/M DNA damage checkpoint by stabilizing the WEE1 Kinase

cell & other

REGULATION

induced by	mitogens
		hypoxia

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in ERBB2-amplified breast carcinomas constitutional     --over   in osteoarthritic cartilage tumoral     --low   in endometrial cancers (Jeong 2009)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     targeting of EFFRI1 in EGFR-low cancer as a promising therapeutic approach

ANIMAL & CELL MODELS